Attempts have been made to use Glial cell line-Derived Neurotrophic Factor (GDNF) that is recognized to exhibit nerve protecting action for the prevention and therapy of neurodegenerative diseases such as Parkinson's disease. However, studies thus far revealed that GDNF has an insufficient effect, so that substances that have more potent nerve protecting action have been demanded for the prevention and therapy of neurodegenerative diseases.
Hepatocyte Growth Factor (HGF) has been found as a potent growth promoting factor for mature hepatocytes and various pharmaceutical activities of it have been reported (Experimental Medicine, Vol. 10, No. 3 (Supplemental Issue) 330-339 (1992)). Further, by making use of its pharmaceutical actions, HGF has been studied and developed as a therapeutic agent for various diseases. On the other hand, the application of an HGF gene to gene therapy has been reported (JP 3-72883 A, WO 97/07824, WO 01/26694).
Actions of HGF on nerves reported based on in-vitro experiments include maintenance of survival and prevention of death of nerve cells of hippocampus neurons, promotion of growth and survival of motor neurons, and maturation and maintenance of survival of dopaminergic neurons, which suggests that the in-vitro action of HGF on nerves is stronger than GDNF.
However, the action of HGF is confirmed only by in-vitro experiments and if some action on nerves is found in-vitro, it cannot be said that nerve protection action is exhibited in-vivo. It has not been studied whether or not HGF has preventive and therapeutic effects on neurodegenerative diseases such as Parkinson's disease.
Further, HGF has a half life in blood as short as about 10 minutes so that it is difficult to maintain its blood level and there has been a problem in the capability of a translocation of an effective amount of HGF to an affected site. The inventor of the present invention has already made it clear that the use of HGF gene in the therapy of various diseases can solve the problems of the half life of HGF and capability of translocation of HGF to the affected site (JP 3-72883 A, WO 97/07824, WO 01/26694).
Therefore, utilization of the HGF gene in the prevention and therapy of neurodegenerative diseases is expected.